Robl in U.S. Pat. No. 5,508,272 disclose compounds of the formula ##STR1## wherein A is ##STR2## as possessing neutral endopeptidase and angiotensin converting enzyme inhibition activity. Among these compounds is [4S-[4.alpha.(R*), 7.alpha., 10a.beta.]]-octahydro-4-[(2-mercapto-1-oxo-3-phenylpropyl)amino]-5-oxo-7H- pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid which is currently undergoing clinical evaluation.
Robl discloses that the amino lactam portion of this compound; i.e., the intermediate ##STR3## can be prepared by coupling an alkyl ester compound such as (S)-2-amino-6,6-dimethoxyhexanoic acid methyl ester with the N-protected amino acid ##STR4## wherein P.sub.1 is an amino protecting group and P.sub.2 is a sulfur protecting group to give the dipeptide of the formula ##STR5## Removal of the P.sub.2 protecting group, followed by acid catalyzed cyclization, and removal of the P.sub.1 protecting group gives [4S-(4.alpha., 7.alpha., 10a.beta.)]-octahydro-4-amino-5-oxo-7H-pyrido[2,1-b][1,3]thiazepine-7-carb oxylic acid, methyl ester.
Robl discloses preparing (S)-2-amino-6,6-dialkoxyhexanoic acid, alkyl ester, such as (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester, by converting N-protected L-.gamma.-hydroxynorleucine to its methyl ester, oxidizing to a corresponding aldehyde, such as of the formula ##STR6## then reacting with trimethyl orthoformate in the presence of a strong acid catalyst, and removing the P.sub.3 protecting group.